The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge
The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge
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DOI：
10.1016/j.jaci.2010.07.006
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发表时间：
2010-10-01
影响因子：
14.2
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
--
作者：
He, Rui;Oyoshi, Michiko K.;Geha, Raif S.
背景：抓挠后皮肤前列腺素（PG）D-2水平升高。在T（H）2细胞受体上表达的趋化因子受体同源分子（CRTH 2）介导对PGD（2）的趋化性，并在T（H）2细胞和嗜酸性粒细胞上表达，这些细胞浸润特应性皮炎患者的皮肤病变。CRTH 2（-/-）小鼠和野生型对照动物通过将卵清蛋白（OVA）重复应用于胶带剥离的皮肤7周来进行表皮致敏，然后通过将OVA应用于胶带剥离的皮肤来进行攻击。剥离先前未致敏的皮肤1周。通过苏木精-伊红染色和免疫组织化学方法评估皮肤组织学。用定量RT-PCR检测细胞因子mRNA的表达。结果：剥带后24小时，皮肤中PGD（2）水平显著升高，而反复致敏的皮肤中PGD（2）水平无明显变化。在CRTH 2（-/-）小鼠中，在用OVA进行慢性表皮致敏的部位，过敏性皮肤炎症正常发生，但在先前用OVA激发的未致敏皮肤中严重受损，如嗜酸性粒细胞和CD 4（+）细胞的皮肤浸润显著减少以及T（H）2细胞因子mRNA表达受损所证明的。在CRTH 2（-/-）小鼠中，在急性OVA激发部位的受损皮肤炎症不是由于对表皮致敏的全身反应受损，因为这些小鼠中的OVA特异性IgG 1和IgE抗体水平以及OVA驱动的脾细胞分泌的细胞因子与野生型对照动物中观察到的相当。在先前致敏的小鼠中，CRTH 2促进过敏性皮肤炎症对皮肤暴露于抗原的响应。（J Allergy Clin Immunol 2010;126：784-90.）
Background: Cutaneous prostaglandin (PG) D-2 levels increase after scratching. Chemoattractant receptor-homologous molecule expressed on receptor on T(H)2 cells (CRTH2) mediates chemotaxis to PGD(2) and is expressed on T(H)2 cells and eosinophils, which infiltrate skin lesions in patients with atopic dermatitis.Objective: We sought to examine the role of CRTH2 in a murine model of atopic dermatitis.Methods: CRTH2(-/-) mice and wild-type control animals were epicutaneously sensitized by means of repeated application of ovalbumin (OVA) to tape-stripped skin for 7 weeks and then challenged by means of OVA application to tape-stripped previously unsensitized skin for 1 week. Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Levels of PGD2, antibody, and cytokines were measured by means of ELISA.Results: PGD(2) levels significantly increased in skin 24 hours after tape stripping, although not in skin subjected to repeated sensitization with OVA. Allergic skin inflammation developed normally at sites of chronic epicutaneous sensitization with OVA in CRTH2(-/-) mice but was severely impaired in previously unsensitized skin challenged with OVA, as evidenced by significantly decreased skin infiltration with eosinophils and CD4(+) cells and impaired T(H)2 cytokine mRNA expression. Impaired skin inflammation at sites of acute OVA challenge in CRTH2(-/-) mice was not due to an impaired systemic response to epicutaneous sensitization because OVA-specific IgG1 and IgE antibody levels and OVA-driven splenocyte secretion of cytokines in these mice were comparable with those seen in wild-type control animals.Conclusions: CRTH2 promotes allergic skin inflammation in response to cutaneous exposure to antigen in previously sensitized mice. (J Allergy Clin Immunol 2010;126:784-90.)